Field of the Invention
The present invention is directed to chewable sustained release compositions and to methods of preparing and using such compositions.
Description of the Related Art
Sustained release compositions have been developed to provide a slow and sustained release of a drug or active ingredient into a subject over an extended period of time. Thus, sustained release compositions mitigate the necessity for multiple daily dosings of certain drugs and other active ingredients. However, most existing sustained release compositions are not suitable as chewable formulations. In fact, chewing most sustained release compositions will inhibit their ability to slowly release the drug or active ingredient over an extended period of time and will result in an uncontrolled burst of the drug or active ingredient. Furthermore, most sustained release compositions have an unacceptable taste when chewed, which decreases the willingness of many patients to accept such tablets.
Chewable tablets of sustained release compositions have been increasingly utilized in various pharmaceutical and veterinary markets due to their ability to sustain constant drug release over an extended time period and maintain taste-masking properties even after being chewed into smaller fragments. For instance, chewable sustained release tablets have developed a niche in veterinary medicine because many of the treated animals tend to chew any medicine given orally. Chewable sustained release tablets are also increasingly being used in human medicine for patients who have difficulties in swallowing or taking intact medications.
Recently, wax-based agents have been incorporated into chewable sustained release compositions in an attempt to provide the desired sustained release and taste-masking properties. For instance, U.S. Patent Application Publication No. 2010/0062988 discloses chewable sustained release compositions produced by using dispersions of the vegetable protein zein coupled with wax-like agents and a spheronizing agent to encapsulate drugs and other active ingredients. The zein/wax matrix is able to produce a chewable sustained release composition that can add a degree of taste-masking to bitter tasting drugs. Similarly, U.S. Patent Application Publication No. 2008/0220079 utilizes wax-like agents in conjunction with a spherizonizing agent to produce a chewable sustained release composition that can encapsulate drugs and other active ingredients. However, the chewable sustained release compositions in both of these publications require that the compositions be heated to a temperature exceeding the melting points of the wax-like agent in order to effectively encapsulate the drug or active ingredient. Unfortunately, this additional heating step can increase the costs of producing these chewable sustained release compositions and potentially damage the encapsulated drug or active ingredient.
U.S. Patent Application Publication No. 2006/0134208 discloses various ingredients used in taste-masking formulations for controlled drug delivery. The low melting point fatty ingredients and amphiphilic ingredients described therein are kneaded or melted together with small amounts of solvent, then granulated into particulates. Following this granulation, the particles are then mixed together and suspended in a hydrophilic water-swellable matrix. The resulting formulations contain a lipophilic matrix surrounded by a hydrophilic matrix. Thus, two independent processes provide for the controlled release mechanism in U.S. 2006/0134208: (1) the dissolution of the hydrophilic matrix and (2) the erosion of the lipophilic matrix. However, the amphiphilic ingredients listed in U.S. 2006/0134208 are not dissolved or dispersed in an alcoholic or hydroalcoholic solution when producing the formulations. Therefore, the amphiphilic ingredients described therein are not contained in a single continuum and do not function as a solid state plasticizer for the ingredients in the lipophilic matrix. Consequently, the separate lipophilic and hydrophilic matrices produced using this process cannot maintain sustained release characteristics when broken or chewed.
Accordingly, there is a need for a chewable sustained release composition, and a process for making such, that is capable of maintaining a sustained release of a drug or active ingredient over an extended time period and that exhibits certain taste-masking properties.